1. Field of the Invention
This invention relates to a method of treating condyloma acuminatum, generally referred to as genital warts or anogenital warts, with a combination of cryosurgery and recombinant DNA human alpha interferon (hIFN-.alpha.). As a result of the combination treatment, the time for patients to have recurrence is significantly prolonged when compared to those treated with cryosurgery alone.
2. Prior Art
Condyloma acuminatum is a venereal disease caused by human papilloma viruses (HPV), including, e.g. Types 6 and 11. The disease is usually referred to as genital warts or anogenital warts. The incidence of the disease is increasing and there is evidence linking HPV infections to genitourinary neoplasms.
Liquid nitrogen is one of the common cryosurgical treatments for condyloma acuminatum. It is topically applied and cryosurgically removes the lesions. Results of such treatment can be temporary and evidence exists that epithelial tissue surrounding the lesion may retain the HPV causative organism causing recurrence of the lesions.
Thus, cryosurgery causes local tissue destruction, but its efficacy is limited and recurrence frequently occurs within a month. As discussed by Ferenczy et al., The New England Journal of Medicine 313; 784-788 (1985), who used laser therapy, the HPV is present in clinically and histologically normal squamous epithelium beyond areas treated destructively. Such presence of the virus in the epithelium was shown to correlate strongly with the risk of recurrence.
Human alpha interferon is a naturally occurring mixture of at least eleven compounds including those designated alpha-1 interferon and alpha-2 interferon. Alpha interferon exhibiting biological properties similar to those of naturally occurring human leukocyte interferon can be made by recombinant methods.
A number of alpha interferon species or components are known and are usually designated by a numeral and letter after the Greek letter alpha. Human alpha-1 interferon is one species contemplated for use in this invention as are the species designated human alpha-2 interferons. Under USAN, recombinant DNA human alpha-2 interferons are designated Interferon Alfa-2a, which can be made as disclosed in Rubenstein, Biochem. Biophys. Acta 695, 5-16 (1982), and Interferon Alfa-2b. Interferon Alfa-2b is the preferred species for use in this invention and is a recombinant DNA human alpha interferon. Also suitable is recombinant DNA human interferon alfa-2a.
Human interferon alfa-2b can be produced in bacteria and other microorganisms using recombinant DNA techniques including those disclosed in Nagata et al. Nature, 284, 316-320 (1980), European Patent No. 32,134 and U.S. Pat. No. 4,289,690. Various alpha interferon species are disclosed in U.S. Pat. No. 4,503,035. The preferred recombinant DNA human interferon alfa-2b used in this invention is also denoted herein as "hIFN.alpha.-2b". Intralesionally administered interferon has been shown to clear about one third of cases of condylomata acuminata when given three times weekly for three weeks as indicated in Eron et al., New England Journal of Medicine 15, 1059-1064, (1986) and Smiles et al., The Biology of the Interferon System 1986, Cantell et al. editor, Dordrecht, Martinus Mijhoff Publishers, 493-501 (1987). Friedman-Kien et al., JAMA 259, 533-538 (1988) reported that intralesional interferon has been shown to clear about two-thirds of cases when given twice weekly for up to eleven weeks.